CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:High-Dose Chemotherapy and Autologous or Allogeneic Transplantation in Aggressive B-Cell Lymphoma-Is There Still a Role?
High-Dose Chemotherapy and Autologous or Allogeneic Transplantation in Aggressive B-Cell Lymphoma-Is There Still a Role?
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CAR-T、BTK抑制剂和PD-1抑制剂等新型疗法改变了侵袭性B细胞淋巴瘤的管理方式。尽管如此,这些新疗法本身也有迟发毒性风险,包括继发恶性肿瘤,并会形成一部分复发、治疗失败或需无限期维持治疗的患者群体。本文讨论自体和异基因干细胞移植在这一背景下的当前作用。对于复发性弥漫大B细胞淋巴瘤患者,CAR-T 细胞治疗在很大程度上已取代自体移植。对于晚期复发患者及部分T细胞丰富型B细胞淋巴瘤患者,应考虑自体移植,因为CAR-T 细胞疗法对后者可能疗效较差。自体移植仍是原发性CNS淋巴瘤患者巩固治疗的首选。在套细胞淋巴瘤中,强化化疗联合BTK抑制剂和利妥昔单抗可取得优良疗效,自体移植的作用正在下降。对于初始化疗失败的霍奇金淋巴瘤患者,自体移植巩固治疗仍为标准治疗。与自体移植相比,异基因移植的复发率较低,但并发症更多、非复发死亡率更高。通常仅用于自体移植失败或无法采集自体干细胞的患者,也可能对CAR-T 治疗失败患者发挥重要作用。侵袭性B细胞淋巴瘤患者照护日益复杂,治疗顺序不断演变,这进一步凸显了合理选择患者和把握干细胞移植最佳时机的重要性。
Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance.
We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining.
In Hodgkin's lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected.
It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation.
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